Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study.

Abstract

Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016. Results Of 75 patients screened, 36 (48.0%) had PD-L1-positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in ≥ 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1-positive endometrial cancer.

• Authors: Patrick A Ott, Yung-Jue Bang, Dominique Berton-Rigaud, Elena Elez, Michael J Pishvaian, Hope S Rugo, Igor Puzanov, Janice M Mehnert, Kyaw L Aung, Juanita Lopez, Marion Carrigan, Sanatan Saraf, Mei Chen, Jean-Charles Soria
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 35 Issue 22 Pg. 2535-2541 (Aug 01 2017) ISSN: 1527-7755 [Electronic] United States
• PMID: 28489510 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• B7-H1 Antigen
• CD274 protein, human
• pembrolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Anorexia (chemically induced)
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• B7-H1 Antigen (analysis)
• Carcinoma (chemistry, drug therapy, genetics, secondary)
• Disease-Free Survival
• Endometrial Neoplasms (chemistry, drug therapy, genetics, pathology)
• Fatigue (chemically induced)
• Female
• Fever (chemically induced)
• Humans
• Microsatellite Instability
• Middle Aged
• Pruritus (chemically induced)
• Response Evaluation Criteria in Solid Tumors
• Retreatment
• Survival Rate